Synergistic anti-inflammatory compositions

ABSTRACT

The present invention is directed to a personal composition comprising a) a strobilurin; b) salicylic acid wherein the ratio of a:b is from about 1:1 to about 100:1; wherein there is a synergistic anti-inflammatory/cellular stress activity.

FIELD OF THE INVENTION

The present invention relates to personal care compositions comprising a strobilurin and salicylic acid demonstrating synergistic anti-inflammatory activity.

BACKGROUND OF THE INVENTION

Optimal health of the hair, scalp and skin is dependent on control of cellular stress and the ability to counteract or remove insults by appropriate protective mechanisms. Cellular stress may be triggered by reactive oxygen species, pollution, toxins, microorganisms, mechanical or chemical insults and several other extrinsic or intrinsic factors. Prolonged, unresolved or high levels of cellular stress is manifested in the decline of hair, scalp or skin health with visible signs of damage (e.g. hair loss, loss of hair or skin pigmentation, scalp or skin dryness, flaking, itching) and both accelerated and chronological aging. Cellular responses to pathological stress converge on inflammation as a major, common mechanism and excessive inflammation contributes to reduced health and several stress-related conditions. Chronic inflammatory disorders of the skin such as dandruff and acne have widespread prevalence, and both involve microorganisms on the skin that produce substances which trigger and exacerbate inflammation.

There is a need for improved products that address and resolve inflammation and cellular stress in chronic disorders of the skin, scalp and hair. Personal care products are also desired that reduce cellular stress and provide consumers with healthier, hair, scalp and skin and enhanced anti-aging benefits.

SUMMARY OF THE INVENTION

The present invention is directed to a personal composition comprising a) a strobilurin; b) salicylic acid wherein the ratio of a:b is from about 1:1 to about 100:1; wherein there is a synergistic anti-inflammatory/cellular stress activity.

DETAILED DESCRIPTION OF THE INVENTION

All percentages and ratios used herein are by weight of the total composition, unless otherwise designated. All measurements are understood to be made at ambient conditions, where “ambient conditions” means conditions at about 25° C., under about one atmosphere of pressure, and at about 50% relative humidity, unless otherwise designated. All numeric ranges are inclusive of narrower ranges; delineated upper and lower range limits are combinable to create further ranges not explicitly delineated.

The compositions of the present invention can comprise, consist essentially of, or consist of, the essential components as well as optional ingredients described herein. As used herein, “consisting essentially of” means that the composition or component may include additional ingredients, but only if the additional ingredients do not materially alter the basic and novel characteristics of the claimed compositions or methods.

As used herein, “comprising” means that other steps and other ingredients which do not affect the end result can be added. This term encompasses the terms “consisting of” and “consisting essentially of”.

As used herein, “mixtures” is meant to include a simple combination of materials and any compounds that may result from their combination.

As used herein, “molecular weight” or “Molecular weight” refers to the weight average molecular weight unless otherwise stated. Molecular weight is measured using industry standard method, gel permeation chromatography (“GPC”).

Where amount ranges are given, these are to be understood as being the total amount of said ingredient in the composition, or where more than one species fall within the scope of the ingredient definition, the total amount of all ingredients fitting that definition, in the composition.

All percentages, parts and ratios are based upon the total weight of the compositions of the present invention, unless otherwise specified. All such weights as they pertain to listed ingredients are based on the active level and, therefore, do not include carriers or by-products that may be included in commercially available materials.

Unless otherwise noted, all component or composition levels are in reference to the active portion of that component or composition, and are exclusive of impurities, for example, residual solvents or by-products, which may be present in commercially available sources of such components or compositions.

It should be understood that every maximum numerical limitation given throughout this specification includes every lower numerical limitation, as if such lower numerical limitations were expressly written herein. Every minimum numerical limitation given throughout this specification will include every higher numerical limitation, as if such higher numerical limitations were expressly written herein. Every numerical range given throughout this specification will include every narrower numerical range that falls within such broader numerical range, as if such narrower numerical ranges were all expressly written herein.

Strobilurins

Strobilurins are a general class of compounds used as agricultural fungicides that are inspired from natural fungal metabolites. Strobilurins are either biosynthesized as a natural product by various Basidiomycete fungi such as Strobilurus tenacellus and Oudemansiella mucida or modeled after natural strobilurins and synthesized with retention of the key β-methoxyacrylate toxophore. Some synthesized strobilurins have a modified toxophore e.g. methyl methoxyiminoacetate or methyl-N-methoxycarbamate. Some synthetic strobilurins are azoxystrobin (CAS number: 131860-33-8), coumoxystrobin (CAS number 850881-70-8), dimoxystrobin (CAS number 149961-52-4), enoxastrobin (CAS number 238410-11-2), fluoxastrobin (CAS number 193740-76-0), kresoxim methyl (CAS number 143390-89-0), mandestrobin (CAS number 173662-97-0), metominostrobin

(CAS number 133408-50-1), orysastrobin (CAS number 248593-16-0), picoxystrobin (CAS number 117428-22-5), pyraclostrobin (CAS number 175013-18-0) pyraoxystrobin (CAS number 862588-11-2), and trifloxystrobin (CAS number 141517-21-7).

Strobilurins control a broad spectrum of plant fungal diseases and are used heavily in crop protection worldwide. They work to inhibit fungal growth by inhibition of mitochondrial respiration. The specific mode of action of strobilurins is by binding the ubiquinol oxidizing site (Q₀ site) in the cytochrome b complex III of the electron transport chain and blocking electron transfer between cytochrome b and cytochrome c₁. Other compounds with this specific mode of action include synthetic and naturally occurring derivatives of the key β-methoxyacrylate toxophore known as oudemansins also first isolated from Oudemansiella mucida, synthetic and naturally occurring myxothiazols from myxobacteria such as Myxococcus flavus, stigmatellins from myxobacteria such as Stigmatella aurantica and the synthetic agricultural chemicals famoxadone and fenamidone.

Azoxystrobin, is an example of an agricultural fungicide belonging to the class of strobilurins. Azoxystrobin as an agricultural fungicide has protectant, curative, eradicant, translaminar and systemic properties and inhibits spore germination and mycelial growth, and also shows antisporulant activity. At labelled application rates, azoxystrobin controls the numerous plant pathogens including Erysiphe graminis, Puccinia spp., Lepiosphaeria nodorum, Septoria tritici and Pyrenophora teres on temperate cereals; Pyricularia oryzae and Rhizoctonia solani on rice; Plasmopara viticola and Uncinula necator on vines; Sphaerotheca fuliginea and Pseudoperonospora cubensis on cucurbitaceae; Phytophthora infestans and Alternaria solani on potato and tomato; Mycosphaerella arachidis, Rhizoctonia solani and Sclerotium rolfsii on peanut; Monilinia spp, and Cladosporium carpophilum on peach; Pythium spp. and Rhizoctonia solani on turf; Mycosphaerella spp. on banana; Cladosporium caryigenum on pecan; Elsinoë fawcetii, Colletotrichum spp. and Guignardia citricarpa on citrus; Colletotrichum spp. and Hemileia vastatrix on coffee. Azoxystrobin is a solid material having low solubility in water.

Some tradenames for azoxystrobin include ABOUND FLOWABLE FUNGICIDE, Aframe, Azoxystar, Azoxyzone, AZteroid 1.65 SC Fungicide, AZURE AGRICULTURAL FUNGICIDE, Endow, QUADRIS FLOWABLE FUNGICIDE, Satori Fungicide, Strobe 2L, and Willowood Azoxy 2SC. Azoxystrobin is commercially available from for example Sigma-Aldrich (St. Louis, Mo.) and Ak Scientific, Inc (Union City, Calif.).

In the present invention, the personal care composition may contain from about 0.02% to about 10% of azoxystrobin; from about 0.05% to about 2% of azoxystrobin; from about 0.1% to about 1% of azoxystrobin.

In the present invention, the personal care composition may contain from about 0.02% to about 10% of a strobilurin; from about 0.05% to about 2% of a strobilurin; from about 0.1% to about 1% of a strobilurin.

Salicylic Acid

Salicylic acid suitable for use in this invention include salicylic acid or a salt thereof. In the present invention such salicylic acid salts may include alkali metal salts, such as sodium and potassium; alkaline earth metal salts, such as calcium and magnesium; ammonium salts; and trialkylammonium salts, such as trimethylammonium and triethylammonium. The present invention may include capryloyl salicylic acid, methyl salicylate, acetyl salicylate, sodium salicylate, choline salicylate, methyl salicylic acid, acetyl salicylic acid, amino salicylic acid, salicylsalicylic acid, menthyl salicylate, phenyl salicylate, amyl salicylate, octyl salicylate, benzyl salicylate, glyceryl salicylate, salicin, salicylaldehyde, salicortin, 2′-O-acetylsalicortin, (−)-tremulacin, saligenin, diflunisal, fendosal, butyloctyl salicylate, C12-15 alkyl salicylate, hexyldodecyl salicylate, isocetyl salicylate, isodecyl salicylate, monoethanolamine salicylate, ethylhexyl salicylate, myristyl salicylate, trolamine salicylate, and tridecyl salicylate The present invention may also include salicylates in the form of natural products such as oil of wintergreen and willow bark extract.

In the present invention, the personal care composition may contain from about 0.1% to about 10% of a salicylic acid; the hair care composition may contain from about 0.3% to about 3% of a salicylic acid; the hair care composition may contain from about 0.5% to about 2% of salicylic acid.

Other Anti-Microbial Actives

The present invention may comprise scalp health agents selected from polyvalent metal salts of pyrithione, and may further comprise one or more anti-fungal or anti-microbial actives. Suitable anti-microbial actives include 2-Pyridinol-N-oxide materials which may include a substituted or unsubstituted 2-pyridinol-N-oxide material or a salt thereof. Included within the scope of this invention are tautomers of this material, e.g., 1-hydroxy-2(1H)-pyridinone and including piroctone olamine, coal tar, sulfur, whitfield's ointment, castellani's paint, aluminum chloride, gentian violet, ciclopirox olamine, undecylenic acid and its metal salts, potassium permanganate, selenium sulfide, sodium thiosulfate, propylene glycol, oil of bitter orange, urea preparations, griseofulvin, 8-Hydroxyquinoline, clioquinol, thiobendazole, thiocarbamates, haloprogin, polyenes, hydroxypyridone, morpholine, benzylamine, allylamines (such as terbinafine), tea tree oil, neem, clove leaf oil, coriander, palmarosa, berberine, thyme red, cinnamon oil, cinnamic aldehyde, citronellic acid, hinokitiol, ichthyol pale, Sensiva SC-50, Elestab HP-100, azelaic acid, lyticase, iodopropynyl butylcarbamate (IPBC), isothiazalinones such as octyl isothiazalinone and azoles, and combinations thereof. The present invention may include anti-microbials such as itraconazole, ketoconazole, selenium sulfide and coal tar.

b. Selenium Sulfide

Selenium sulfide is a particulate scalp health agent suitable for use in the anti-microbial compositions of the present invention. Selenium sulfide is generally regarded as a compound having one mole of selenium and two moles of sulfur, although it may also be a cyclic structure that conforms to the general formula Se_(x)S_(y), wherein x+y=8. Average particle diameters for the selenium sulfide are typically less than 15 μm, as measured by forward laser light scattering device (e.g. Malvern 3600 instrument), and may be in the present invention, less than 10 μm. Selenium sulfide compounds are described, for example, in U.S. Pat. No. 2,694,668; U.S. Pat. No. 3,152,046; U.S. Pat. No. 4,089,945; and U.S. Pat. No. 4,885,107.

c. Sulfur

Sulfur may also be used as a particulate anti-microbial/scalp health agent in the anti-microbial compositions of the present invention.

Additional Anti-Microbial Actives

Additional anti-microbial actives of the present invention may include extracts of melaleuca (tea tree) and charcoal. The present invention may also comprise combinations of anti-microbial actives. Such combinations may include piroctone olamine and zinc pyrithione combinations, pine tar and sulfur combinations, salicylic acid and zinc pyrithione combinations, piroctone olamine and climbazole combinations, and salicylic acid and piroctone olamine combinations, zinc pyrithione and climbazole and mixtures thereof.

In the present invention, the scalp health agent may be present in an amount from about 0.01% to 10%, may be from about 0.1% to 9%, may be from about 0.25% to 8%, may be from about 0.5% to 6%.

In the present invention, the composition comprises an effective amount of a zinc-containing layered material. Zinc-containing layered materials may be those with crystal growth primarily occurring in two dimensions. It is conventional to describe layer structures as not only those in which all the atoms are incorporated in well-defined layers, but also those in which there are ions or molecules between the layers, called gallery ions (A. F. Wells “Structural Inorganic Chemistry” Clarendon Press, 1975). Zinc-containing layered materials (ZLMs) may have zinc incorporated in the layers and/or be components of the gallery ions. The following classes of ZLMs represent relatively common examples of the general category and are not intended to be limiting as to the broader scope of materials which fit this definition.

Many ZLMs occur naturally as minerals. In the present invention, the ZLM may be selected from the group consisting of: hydrozincite (zinc carbonate hydroxide), basic zinc carbonate, aurichalcite (zinc copper carbonate hydroxide), rosasite (copper zinc carbonate hydroxide), and mixtures thereof. Related minerals that are zinc-containing may also be included in the composition. Natural ZLMs can also occur wherein anionic layer species such as clay-type minerals (e.g., phyllosilicates) contain ion-exchanged zinc gallery ions. All of these natural materials can also be obtained synthetically or formed in situ in a composition or during a production process.

Another common class of ZLMs, which are often, but not always, synthetic, is layered double hydroxides. In the present invention, the ZLM may be a layered double hydroxide conforming to the formula [M²⁺ _(1−x)M³⁺ _(x)(OH)₂]^(x+)A^(m−) _(x/m)·nH₂O wherein some or all of the divalent ions (M²⁺) are zinc ions (Crepaldi, E L, Pava, P C, Tronto, J, Valim, J B J. Colloid Interfac. Sci. 2002, 248, 429-42).

Yet another class of ZLMs can be prepared called hydroxy double salts (Morioka, H., Tagaya, H., Karasu, M, Kadokawa, J, Chiba, K Inorg. Chem. 1999, 38, 4211-6). In the present invention, the ZLM may be a hydroxy double salt conforming to the formula [M²⁺ _(1−x)M²⁺ _(1−x)(OH)_(3(1−y))]⁺A^(n−) _((1=3y)/n)·nH₂O where the two metal ions (M²⁺) may be the same or different. If they are the same and represented by zinc, the formula simplifies to [Zn_(1+x)(OH)₂]^(2x+)2x A⁻·nH₂O. This latter formula represents (where x=0.4) materials such as zinc hydroxychloride and zinc hydroxynitrate. In the present invention, the ZLM may be zinc hydroxychloride and/or zinc hydroxynitrate. These are related to hydrozincite as well wherein a divalent anion replace the monovalent anion. These materials can also be formed in situ in a composition or in or during a production process.

In the present invention, the composition may comprise basic zinc carbonate. Commercially available sources of basic zinc carbonate include Zinc Carbonate Basic (Cater Chemicals: Bensenville, Ill., USA), Zinc Carbonate (Shepherd Chemicals: Norwood, Ohio, USA), Zinc Carbonate (CPS Union Corp.: New York, N.Y., USA), Zinc Carbonate (Elementis Pigments: Durham, UK), and Zinc Carbonate A C (Bruggemann Chemical: Newtown Square, Pa., USA). Basic zinc carbonate, which also may be referred to commercially as “Zinc Carbonate” or “Zinc Carbonate Basic” or “Zinc Hydroxy Carbonate”, is a synthetic version consisting of materials similar to naturally occurring hydrozincite. The idealized stoichiometry is represented by Zn₅(OH)₆(CO₃)₂ but the actual stoichiometric ratios can vary slightly and other impurities may be incorporated in the crystal lattice.

In the present invention, the composition may comprise an effective amount of a zinc-containing layered material. In the present invention, the composition may comprise from about 0.001% to about 10%, or from about 0.01% to about 7%, or from about 0.1% to about 5% of a zinc-containing layered material, by total weight of the composition.

The present invention may have a zinc-containing layered material and a pyrithione or polyvalent metal salt of pyrithione, the ratio of zinc-containing layered material to pyrithione or a polyvalent metal salt of pyrithione is from about 5:100 to about 10:1, or from about 2:10 to about 5:1, or from about 1:2 to about 3:1.

PGE-2 Assay

Inhibiting the Cell's Inflammation Response to a Stressor—Prostaglandin E2 (“PGE2”) Assay.

This example demonstrates the ability of strobilurins and salicylic acid combinations to inhibit PGE2 activation in a synergistic manner at some specific ratios. PGE2 is a hormone-like substance that is known to participate in modulation of inflammation. Cellular inflammation is associated with a variety of hair, skin and scalp conditions, and thus inhibiting PGE2 activation vis-à-vis cellular inflammation may help treat these types of hair, skin and scalp conditions.

Method

TERT keratinocytes (“tKC”-tKCs are human keratinocytes which have been transfected with the human telomerase reverse transcriptase gene to immortalize the cells) are obtained from Jerry Shay, University of Texas, Southwestern and plated at 40,000 cells/well into 24-well plates in 1 ml/well volume. EpiLife Medium (Life Technologies cat # MEPICFPRF500) supplemented with keratinocyte growth supplement (Life technologies cat #S-001-5) is used as the assay media. The cells are grown to confluence/near confluence, (typically 24 hours after plating 40,000 cells/well in 24 well plate) and then subjected to 15 mJ/cm² UVB-stress (typically 14-16 exposure time in BioSun). The test compositions (strobilurins, salicylic acid, strobilurins+salicylic acid, and positive control 10 uM idebenone) are added to replace the medium (EpiLife Medium with 0.1% final concentration of DMSO-briefly, 1000× stocks of actives and combinations made in 100% DMSO and diluted into Epilife media 1 to 1000), and the plates are incubated for 18-24 hours. The supernatant is removed from each well, and the cells are rinsed with 2 ml/well medium (without supplements). A Cell Titer-Glo assay (Promega cat # G7571; Madison Wis.) is used to measure ATP activity, is conducted on the cells for normalization. The supernatant is tested in a PGE2 assay (Prostaglandin E2 Assay kit from Cisbio Bioassays cat# 62P2APEB) according to the manufacturer's instructions. The PGE2 results are normalized to ATP activity. The PGE2 quantitation (pg/mL) from the supernatant is divided by the normalization factor (treatment ATP/control ATP).

Example Calculation to Compute PGE2 Inhibition by Strobilurin

Luminescence of vehicle control in ATP assay=704567

Luminescence of strobilurin treatment in ATP assay=678903

Normalization factor for strobilurin treatment=1.038

PGE2 quantitation for vehicle control=2458 pg/mL PGE2

PGE2 quantitation for strobilurin treatment=2347 pg/mL PGE2

Normalized PGE2 values

-   -   control=2458/1=2458     -   strobilurin=2347/1.038=2261%

% inhibition for strobilurin=[100×(2458−2347)/2458]=8%

Student's T-Test (equal variance, 2 sided) are used to calculate p-values between observed combinations and expected combinations with p-value <0.05 considered statistically significant. Expected combination values are calculated by adding the PGE2 inhibition values of strobilurins alone and salicylic acid alone. Synergy factor is simply the ratio of observed combination/expected combination. Synergy factors greater than 1.0 with a p-value <0.05 are deemed synergistic.

The conclusion of the PGE2 experiments is that even though strobilurins and salicylic acid are relatively weak materials individually in inhibiting PGE2 release from keratinocytes at these levels, combinations of strobilurins and salicylic acid do in fact surprisingly suppress PGE2 release. Other strobilurins also synergistically inhibit PGE2 release as well. Multiple ratios of azoxystrobin to salicylic acid have been tested to define the ratios at which the synergistic inhibition of PGE2 release occurs and at Azoxystrobin: salicylic acid ratio of 1:1 and 50:1 there is statistically significant synergy. At Azoxystrobin: salicylic acid ratio of 1:10 and 100:1, there is not statistically significant synergy, but the combination does in fact show additivity in reducing PGE2 release at these ratios.

In the present invention, another strobilurin and salicylic acid may demonstrate that combinations of a strobilurin and salicylic acid do in fact also surprisingly suppress PGE2 release in a synergistic manner. Synergistic inhibition of PGE2 release occurs with combinations of trifloxystrobin and salicylic acid at 50:1, orysastrobin and salicylic acid between 1:1 and 50:1, kresoxim methyl and salicylic acid at 50:1, dimoxystrobin and salicylic acid at 50:1, fluoxastrobin and salicylic acid at 10:1 and 50:1, and picoxystrobin and salicylic acid at 10:1 to 100:1.

strobilurin w/v % 1 × 10−7 1 × 10−7 1 × 10−6 5 × 10−6 1 × 10−5 salicylic acid 1 × 10−6 1 × 10−7 1 × 10−7 1 × 10−7 1 × 10−7 strobilurin:salicylic acid ratio 1:10 1:1 10:1 50:1 100:1 Treatment % PGE2 Inhibition azoxystrobin 8 8 22 37 58 salicylic acid 32 18 18 18 18 azoxystrobin + salicylic acid 34 44 68 76 73 (observed) azoxystrobin + salicylic 40 26 40 55 76 acid(expected) synergy factor 0.85 1.69 1.70 1.38 0.96 p-value observed vs expected 0.55 0.023* 0.008* 0.012* 0.82 trifloxystrobin 5 5 7 8 8 salicylic acid 32 18 18 18 18 trifloxystrobin + salicylic 32 23 28 42 25 acid(ob served) trifloxystrobin + salicylic acid 37 23 25 26 26 (expected) synergy factor 0.86 1.00 1.12 1.62 0.96 p-value observed vs expected 0.45 0.97 0.78 0.032* 0.91 orysastrobin 6 6 12 18 36 salicylic acid 32 18 18 18 18 orysastrobin + salicylic acid 39 42 50 54 57 (observed) orysastrobin + salicylic 38 24 30 36 54 acid(expected) synergy factor 1.03 1.75 1.67 1.50 1.06 p-value observed vs expected 0.95 0.033* 0.014* 0.022* 0.78 kresoxim methyl 5 5 7 9 12 salicylic acid 32 18 18 18 18 kresoxim methyl + salicylic 34 22 28 42 33 acid (observed) kresoxim methyl + salicylic 37 23 25 27 30 acid (expected) synergy factor 0.92 0.96 1.12 1.56 1.10 p-value observed vs expected 0.78 0.95 0.81 0.037* 0.78 dimoxystrobin 4 4 7 11 13 salicylic acid 32 18 18 18 18 dimoxystrobin + salicylic acid 34 19 25 45 30 (observed) dimoxystrobin + salicylic 36 22 25 29 31 acid(expected) synergy factor 0.94 0.86 1.00 1.55 0.97 p-value observed vs expected 0.78 0.82 0.96 0.028* 0.87 fluoxastrobin 5 5 9 17 42 salicylic acid 32 18 18 18 18 fluoxastrobin + salicylic 35 26 47 53 58 acid(observed) fluoxastrobin + salicylic acid 37 23 27 35 60 (expected) synergy factor 0.95 1.13 1.74 1.51 0.97 p-value observed vs expected 0.75 0.67 0.023* 0.032* 0.78 picoxystrobin 6 6 12 18 24 salicylic acid 32 18 18 18 18 picoxystrobin + salicylic 40 26 55 63 59 acid(observed) picoxystrobin + salicylic acid 38 24 30 36 42 (expected) synergy factor 1.05 1.08 1.83 1.75 1.40 p-value observed vs expected 0.91 0.84 0.007* 0.012* 0.032* pyraclostrobin 30.4 30.4 46.0 55.3 70.4 salicylic acid 31.4 16.2 16.2 16.2 16.2 pyraclostrobin + salicylic 60.4 45.6 58.7 67.1 72.1 acid(ob served) pyraclostrobin + salicylic acid 61.8 46.6 62.2 71.5 86.6 (expected) synergy factor 0.98 0.98 0.94 0.94 0.83 p-value observed vs expected 0.89 0.97 0.73 0.67 0.61 *indicates statistical significance (p value < 0.05 between observed and expected). The top table contains the ranges for strobilurins with salicylic acid.

Strobilurin:Salicylic acid 10:1 1:1 1:10 1:50 1:100 Molar Ratios azoxystrobin 0.0342 0.342 3.42 17.1 34.2 trifloxystrobin 0.0338 0.338 3.38 16.9 33.8 orysastrobin 0.0353 0.353 3.53 17.6 35.3 kresoxim methyl 0.0441 0.441 4.41 22.0 44.1 dimoxystrobin 0.0423 0.423 4.23 21.2 42.3 fluoxastrobin 0.0301 0.301 3.01 15.1 30.1 picoxystrobin 0.0376 0.376 3.76 18.8 37.6 pyraclostrobin 0.0356 0.356 3.56 17.8 35.6

In the present invention a personal composition may comprise a) a strobilurin; b) salicylic acid wherein the ratio of a:b is from about 1:1 to about 100:1; wherein there is a synergistic anti-inflammatory/cellular stress activity. The present invention may comprise a method of using a composition comprising a) a strobilurin; b) salicylic acid; wherein the ratio of a:b is from about 1:1 to about 100:1 to provide a synergistic anti-inflammatory/cellular stress activity. The present invention may comprise a method of using a composition comprising: a)) a strobilurin; b) salicylic acid; wherein the ratio of a:b is from about 1:1 to about 100:1 to provide a synergistic anti-inflammatory/cellular stress activity wherein there is at least about a 20% reduction in PGE2 release compared to a baseline. The present invention may comprise a method wherein at least about a 40% reduction in PGE2 release compared to a baseline. The present inventions may comprise use of strobilurins and salicylic acid in a personal care composition for improving inflammation and cellular stress conditions in skin, scalp and hair. The present invention may comprise use of strobilurins and salicylic acid in a personal care composition for an anti-inflammatory benefit.

Detersive Surfactant

The present invention may be present in the form of a shampoo, conditioner, or leave on treatment. The shampoo composition may comprise one or more detersive surfactants, which provides cleaning performance to the composition. The one or more detersive surfactants in turn may comprise an anionic surfactant, amphoteric or zwitterionic surfactants, or mixtures thereof. Various examples and descriptions of detersive surfactants are set forth in U.S. Pat. No. 6,649,155; U.S. Patent Application Publication No. 2008/0317698; and U.S. Patent Application Publication No. 2008/0206355, which are incorporated herein by reference in their entirety.

The concentration of the detersive surfactant component in the shampoo composition should be sufficient to provide the desired cleaning and lather performance, and generally ranges from about 2 wt % to about 50 wt %, from about 5 wt % to about 30 wt %, from about 8 wt % to about 25 wt %, from about 10 wt % to about 20 wt %, about 5 wt %, about 10 wt %, about 12 wt %, about 15 wt %, about 17 wt %, about 18 wt %, or about 20 wt %.

Anionic surfactants suitable for use in the compositions are the alkyl and alkyl ether sulfates. Other suitable anionic surfactants are the water-soluble salts of organic, sulfuric acid reaction products. Still other suitable anionic surfactants are the reaction products of fatty acids esterified with isethionic acid and neutralized with sodium hydroxide. Other similar anionic surfactants are described in U.S. Pat. Nos. 2,486,921; 2,486,922; and 2,396,278, which are incorporated herein by reference in their entirety.

Exemplary anionic surfactants for use in the shampoo composition include ammonium lauryl sulfate, ammonium laureth sulfate, triethylamine lauryl sulfate, triethylamine laureth sulfate, triethanolamine lauryl sulfate, triethanolamine laureth sulfate, monoethanolamine lauryl sulfate, monoethanolamine laureth sulfate, diethanolamine lauryl sulfate, diethanolamine laureth sulfate, lauric monoglyceride sodium sulfate, sodium lauryl sulfate, sodium laureth sulfate, potassium lauryl sulfate, potassium laureth sulfate, sodium lauryl sarcosinate, sodium lauroyl sarcosinate, lauryl sarcosine, cocoyl sarcosine, ammonium cocoyl sulfate, ammonium lauroyl sulfate, sodium cocoyl sulfate, sodium lauroyl sulfate, potassium cocoyl sulfate, potassium lauryl sulfate, triethanolamine lauryl sulfate, triethanolamine lauryl sulfate, monoethanolamine cocoyl sulfate, monoethanolamine lauryl sulfate, sodium tridecyl benzene sulfonate, sodium dodecyl benzene sulfonate, sodium cocoyl isethionate and combinations thereof. The anionic surfactant may be sodium lauryl sulfate or sodium laureth sulfate.

Suitable amphoteric or zwitterionic surfactants for use in the shampoo composition herein include those which are known for use in shampoo or other personal care cleansing. Concentrations of such amphoteric surfactants range from about 0.5 wt % to about 20 wt %, and from about 1 wt % to about 10 wt %. Non limiting examples of suitable zwitterionic or amphoteric surfactants are described in U.S. Pat. Nos. 5,104,646 and 5,106,609, which are incorporated herein by reference in their entirety.

Amphoteric detersive surfactants suitable for use in the shampoo composition include those surfactants broadly described as derivatives of aliphatic secondary and tertiary amines in which the aliphatic radical can be straight or branched chain and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic group such as carboxy, sulfonate, sulfate, phosphate, or phosphonate. Exemplary amphoteric detersive surfactants for use in the present shampoo composition include cocoamphoacetate, cocoamphodiacetate, lauroamphoacetate, lauroamphodiacetate, and mixtures thereof.

Zwitterionic detersive surfactants suitable for use in the shampoo composition include those surfactants broadly described as derivatives of aliphatic quaternaryammonium, phosphonium, and sulfonium compounds, in which the aliphatic radicals can be straight or branched chain, and wherein one of the aliphatic substituents contains from about 8 to about 18 carbon atoms and one contains an anionic group such as carboxy, sulfonate, sulfate, phosphate or phosphonate. Further, zwitterionics such as betaines may be selected.

Non limiting examples of other anionic, zwitterionic, amphoteric or optional additional surfactants suitable for use in the shampoo composition are described in McCutcheon's, Emulsifiers and Detergents, 1989 Annual, published by M. C. Publishing Co., and U.S. Pat. Nos. 3,929,678, 2,658,072; 2,438,091; 2,528,378, which are incorporated herein by reference in their entirety.

The shampoo composition may also comprise a shampoo gel matrix, an aqueous carrier, and other additional ingredients described herein.

Aqueous Carrier

The shampoo composition comprises a first aqueous carrier. Accordingly, the formulations of the shampoo composition can be in the form of pourable liquids (under ambient conditions). Such compositions will therefore typically comprise a first aqueous carrier, which is present at a level of at least 20 wt %, from about 20 wt % to about 95 wt %, or from about 60 wt % to about 85 wt %. The first aqueous carrier may comprise water, or a miscible mixture of water and organic solvent, and in one aspect may comprise water with minimal or no significant concentrations of organic solvent, except as otherwise incidentally incorporated into the composition as minor ingredients of other components.

The first aqueous carriers useful in the shampoo composition include water and water solutions of lower alkyl alcohols and polyhydric alcohols. The lower alkyl alcohols useful herein are monohydric alcohols having 1 to 6 carbons, in one aspect, ethanol and isopropanol. The polyhydric alcohols useful herein include propylene glycol, hexylene glycol, glycerin, and propane diol.

A. Aqueous Carrier

The conditioner gel matrix of the conditioner composition includes a second aqueous carrier. Accordingly, the formulations of the conditioner composition can be in the form of pourable liquids (under ambient conditions). Such compositions will therefore typically comprise a second aqueous carrier, which is present at a level of from about 20 wt % to about 95 wt %, or from about 60 wt % to about 85 wt %. The second aqueous carrier may comprise water, or a miscible mixture of water and organic solvent, and in one aspect may comprise water with minimal or no significant concentrations of organic solvent, except as otherwise incidentally incorporated into the composition as minor ingredients of other components.

The second aqueous carriers useful in the conditioner composition include water and water solutions of lower alkyl alcohols and polyhydric alcohols. The lower alkyl alcohols useful herein are monohydric alcohols having 1 to 6 carbons, in one aspect, ethanol and isopropanol. The polyhydric alcohols useful herein include propylene glycol, hexylene glycol, glycerin, and propane diol.

Additional Components

The shampoo composition, conditioner compositions, and/or leave-on treatments described herein may comprise one or more additional components known for use in hair care or personal care products, provided that the additional components are physically and chemically compatible with the essential components described herein, or do not otherwise unduly impair product stability, aesthetics or performance. Such additional components are most typically those described in reference books such as the CTFA Cosmetic Ingredient Handbook, Second Edition, The Cosmetic, Toiletries, and Fragrance Association, Inc. 1988, 1992. Individual concentrations of such additional components may range from about 0.001 wt % to about 10 wt % by weight of the hair care compositions.

Non-limiting examples of additional components for use in the hair care compositions include conditioning agents , natural cationic deposition polymers, synthetic cationic deposition polymers, anti-dandruff agents, particles, suspending agents, paraffinic hydrocarbons, propellants, viscosity modifiers, dyes, non-volatile solvents or diluents (water-soluble and water-insoluble), pearlescent aids, foam boosters, additional surfactants or nonionic cosurfactants, pediculocides, pH adjusting agents, perfumes, preservatives, proteins, skin active agents, sunscreens, UV absorbers, and vitamins.

1. Conditioning Agent

The hair care compositions may comprise one or more conditioning agents. Conditioning agents include materials that are used to give a particular conditioning benefit to hair. The conditioning agents useful in the hair care compositions of the present invention typically comprise a water-insoluble, water-dispersible, non-volatile, liquid that forms emulsified, liquid particles. Suitable conditioning agents for use in the hair care composition are those conditioning agents characterized generally as silicones, organic conditioning oils or combinations thereof, or those conditioning agents which otherwise form liquid, dispersed particles in the aqueous surfactant matrix.

One or more conditioning agents are present from about 0.01 wt % to about 10 wt %, from about 0.1 wt % to about 8 wt %, and from about 0.2 wt % to about 4 wt %, by weight of the composition.

Silicone Conditioning Agent

The compositions of the present invention may contain one or more silicone conditioning agents. Examples of the silicones include dimethicones, dimethiconols, cyclic silicones, methylphenyl polysiloxane, and modified silicones with various functional groups such as amino groups, quaternary ammonium salt groups, aliphatic groups, alcohol groups, carboxylic acid groups, ether groups, epoxy groups, sugar or polysaccharide groups, fluorine-modified alkyl groups, alkoxy groups, or combinations of such groups. Such silicones may be soluble or insoluble in the aqueous (or non-aqueous) product carrier. In the case of insoluble liquid silicones, the polymer can be in an emulsified form with droplet size of about 10 nm to about 30 micrometers

Organic Conditioning Materials

The conditioning agent of the compositions of the present invention may also comprise at least one organic conditioning material such as oil or wax, either alone or in combination with other conditioning agents, such as the silicones described above. The organic material can be nonpolymeric, oligomeric or polymeric. It may be in the form of oil or wax and may be added in the formulation neat or in a pre-emulsified form. Some non-limiting examples of organic conditioning materials include, but are not limited to: i) hydrocarbon oils; ii) polyolefins, iii) fatty esters, iv) fluorinated conditioning compounds, v) fatty alcohols, vi) alkyl glucosides and alkyl glucoside derivatives; vii) quaternary ammonium compounds; viii) polyethylene glycols and polypropylene glycols having a molecular weight of up to about 2,000,000 including those with CTFA names PEG-20 200, PEG-400, PEG-600, PEG-1000, PEG-2M, PEG-7M, PEG-14M, PEG-45M and mixtures thereof.

Benefit Agents

The hair care composition may further comprise one or more additional benefit agents. The benefit agents comprise a material selected from the group consisting of anti-dandruff agents, anti-fungal agents, anti-itch agents, anti-bacterial agents, anti-microbial agents, moisturization agents, anti-oxidants, vitamins, lipid soluble vitamins, perfumes, brighteners, enzymes, sensates, attractants, dyes, pigments, bleaches, and mixtures thereof.

The hair care compositions of the present invention may be presented in typical hair care formulations. They may be in the form of solutions, dispersion, emulsions, powders, talcs, encapsulated, spheres, spongers, solid dosage forms, foams, and other delivery mechanisms. The compositions of the present invention may be hair tonics, leave-on hair products such as treatment, and styling products, rinse-off hair products such as shampoos, and treatment products; and any other form that may be applied to hair.

The hair care compositions are generally prepared by conventional methods such as are known in the art of making the compositions. Such methods typically involve mixing of the ingredients in one or more steps to a relatively uniform state, with or without heating, cooling, application of vacuum, and the like. The compositions are prepared such as to optimize stability (physical stability, chemical stability, photostability) and/or delivery of the active materials. The hair care composition may be in a single phase or a single product, or the hair care composition may be in a separate phases or separate products. If two products are used, the products may be used together, at the same time or sequentially. Sequential use may occur in a short period of time, such as immediately after the use of one product, or it may occur over a period of hours or days.

The present invention may be directed to use of strobilurins in a personal care composition for improving inflammation and cellular stress conditions in skin, scalp and hair. The present invention may be directed to use of strobilurins in a personal care composition for an anti-inflammatory benefit. The present invention may be directed to use of strobilurins as claimed in present claim set for anti-inflammatory benefit.

EXAMPLES

Non-Limiting Examples

The shampoo compositions illustrated in the following examples are prepared by conventional formulation and mixing methods. All exemplified amounts are listed as weight percents on an active basis and exclude minor materials such as diluents, preservatives, color percentages are based on weight unless otherwise specified.

Shampoo Examples

Example Note Component 1 2 3 4 Water 79.09 81.9 83.1 80.5 1 Sodium laureth-1 sulfate 11 14 0 6 2 Cocamidopropyl betaine 1 0 0 7 3 CMEA 1 2 0 0 4 Sodium lauroyl sarcosinate 0 0 5 0 5 Decyl glucoside 0 0 5 0 6 Sodium laureth sulfosuccinate 0 0 3 0 7 Hydroxypropyl Methylcellulose 0.3 0.1 0.2 0 8 1,10-Decanediol 0 0 0.1 0 9 Salicylic Acid 0.2 1.0 1.8 3.0 Azoxystrobin 0 1.0 0 3.0 Orysastrobin 0 0 1.8 0 Picoxystrobin 2.0 0 0 0 10 Ethylene glycol distearate 1.8 0 0 0 11 Dimethiconol 1 0 0 0 All above are on active basis; e.g. 11% SLE1S would require an addition of 44% of a 25% active SLE1S solution. The below table explains each Note from the above table

1 Supplied at 25% active by Stepan 2 Supplied at 30% active by Evonik 3 Supplied at 85% active by BASF 4 Supplied at 30% active by Croda 5 Supplied as 50% active by BASF 6 Supplied as 35% active by Solvay 7 Supplied by Dow 8 Supplied by Symrise 9 Supplied by Ampak Company 10 Supplied by Evonik 11 Supplied by Wacker

The following examples further describe and demonstrate examples within the scope of the present invention. The examples are given solely for the purpose of illustration and are not to be construed as limitations of the present invention, as many variations thereof are possible without departing from the spirit and scope of the invention. Where applicable, ingredients are identified by chemical or CTFA name, or otherwise defined below.

Conditioner Compositions (wt %) Components Ex.5 Ex.6 Ex. 7 Ex. 8 Ex. 9 Ex. 10 Behenyl 3.42 3.42 2.85 3.42 trimethylammonium Chloride/IPA*1 Stearylamidopropyl 2.40 2.40 dimethylamine Polysorbate 20 0.03 0.03 L-glutamic acid 0.77 0.77 Citric acid 0.22 0.10 0.20 0.30 0.06 0.22 Cetyl alcohol 1.67 1.67 2.50 2.50 1.67 1.67 Stearyl alcohol 4.18 4.18 4.50 4.50 4.18 4.18 Salicylic Acid 0.25 1.80 0.50 0.25 3.0 1.8 Azoxystrobin 0 1.8 0.5 0.25 3.0 0 Orysastrobin 0.25 0 0 0 0 1.8 Benzyl alcohol 0.4 0.4 0.4 0.4 0.4 0.4 Phenoxy ethanol 0.4 0.4 0.4 0.4 0.4 0.4 Sodium benzoate 0.25 0.25 0.25 0.25 0.25 0.25 Polydimethylsiloxane 3.00 0.85 1.40 Deionized Water q.s. to 100% pH 4.1 4.9 5.0 4.2 5.9 5.9

Leave-On Treatment Examples

Component Note Example 11 12 13 14 15 16 17 18 19 20 Water 62.55 62.7 51.7 49.75 45.6 48.85 38.1 39.7 32.95 32.8 1 Ethanol 30 30 40 40 40 40 5 50 50 50 2 2-Pyrrolidinone, 3.5 3.5 4 4 4 4 4 4 4 4 1-ethenyl-, homopolymer Azoxystrobin 0.25 0 0.5 0 1.0 0 1.8 0 3.0 0 Orysastrobin 0 0.25 0 0.5 0 1.0 0 1.8 0 3.0 3 Hydroxypropyl 0 0 0 2 0 0 0 0 2 0 Methylcellulose 4 Hydroxypropyl 0 0 0 0 5 0 0 0 0 3 Starch Phosphate 5 Menthol 0.25 0.3 0.3 0.25 0.4 0.25 0.3 0.3 0.25 0.4 6 Salicylic acid 0.25 0.25 0.5 0.5 1.0 1.0 1.8 1.8 3.0 3.0 7 Niacinamide 2.5 2.5 2.5 2.5 2.5 2.5 2.5 0 2.5 2.5 8 Caffeine 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0 0.1 9 Panthenol 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0.1 0 10 PEG-40 0 0 0 0 0 1 1 1 1 1 Hydrogenated Castor Oil 11 Propylene Glycol 0 0 0 0 0 0.9 0 0.9 0.9 0 Fragrance 0.5 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.3 0.2

-   1 SD-40B 200 Alcohol from Pride Solvents -   2 Flexithix from Ashland -   3 Benecel K200M from Ashland -   4 Structure XL from AkzoNobel -   5 Menthol from Kerry Ingredients and Flavors -   6 Salicylic acid from Ampak Company -   7 Niacinamide from Lonza -   8 Caffeine from Merck -   9 D-Panthenol from BASF -   10 Cremophor RH-40 from BASF -   11 Propylene Glycol from Sigma Aldrich

Combinations

-   Paragraph A. A personal composition comprising:     -   a) a strobilurin;     -   b) salicylic acid     -   wherein the ratio of a:b is from about 1:1 to about 100:1;         wherein there is a synergistic anti-inflammatory/cellular stress         activity. -   Paragraph B A personal care composition according to Paragraph A     wherein the anti-inflammatory benefit is measured as Prostaglandin     E2 (PGE2) activity. -   Paragraph C A personal care composition according to Paragraph A-B     wherein the strobilurin is selected from the group consisting of     azoxystrobin, trifloxystrobin, orysastrobin, kresoxim methyl,     dimoxystrobin, fluoxastrobin, picoxystrobin and mixtures thereof. -   Paragraph D A personal care composition according to Paragraph A-C     wherein the ratio of azoxystrobin: salicylic acid ratio is from     about 1:1 to about 50:1. -   Paragraph E A personal care composition according to Paragraph A-D     wherein the ratio of trifloxystrobin: salicylic acid is at about     50:1. -   Paragraph F A personal care composition according to Paragraph A-E     wherein the ratio of orysastrobin: salicylic acid is from about 1:1     to about 50:1. -   Paragraph G A personal care composition according to Paragraph A-F     wherein the ratio of kresoxim methyl :salicylic acid is at about     50:1. -   Paragraph H A personal care composition according to Paragraph A-G     wherein the ratio of dimoxystrobin: salicylic acid is at about 50:1. -   Paragraph I A personal care composition according to Paragraph A-H     wherein the ratio of fluoxastrobin:salicylic acid is from about 10:1     to about 50:1. -   Paragraph J A persona care composition according to Paragraph A-I     wherein the ratio of picoxystrobin and salicylic acid is from about     10:1 to about 100:1. -   Paragraph K A personal care composition according to Paragraph A-J     wherein the personal care composition is selected from group     consisting of a shampoo, conditioner, leave-on, tonic and mixtures     thereof. -   Paragraph L A personal care composition according to Paragraph A-K     wherein the strobilurin is from about 0.02% to about 10%. -   Paragraph M A personal care composition according to Paragraph A-L     wherein the salicylic acid is from about 0.1% to about 10%, by     weight of the composition. -   Paragraph N A personal care composition according to Paragraph A-M     wherein the salicylic acid is 0.5% to about 2%, by weight of the     composition. -   Paragraph O A method of using a composition according to Paragraph     A-N comprising     -   a) a strobilurin;     -   b) salicylic acid;     -   wherein the ratio of a:b is from about 1:1 to about 100:1 to         provide a synergistic anti-inflammatory/cellular stress         activity. -   Paragraph P A method of using a composition according to Paragraph     A-O comprising:     -   a)) a strobilurin;     -   b) salicylic acid;     -   wherein the ratio of a:b is from about 1:1 to about 100:1 to         provide a synergistic anti-inflammatory/cellular stress activity         wherein there is at least about a 20% reduction in PGE2 release         compared to a baseline. -   Paragraph Q A method according to Paragraph A-P wherein the is at     least about a 40% reduction in PGE2 release compared to a baseline. -   Paragraph R Use of strobilurins and salicylic acid according to     Paragraph A-Q in a personal care composition according to claim 1     for improving inflammation and cellular stress conditions in skin,     scalp and hair. -   Paragraph S Use of strobilurins and salicylic acid according to     Paragraph A-R in a personal care composition according to claim 1     for an anti-inflammatory benefit.

Product Forms

The personal care compositions of the present invention may be presented in typical personal care formulations. They may be in the form of solutions, dispersion, emulsions, powders, talcs, encapsulated, spheres, spongers, solid dosage forms, foams, and other delivery mechanisms. The compositions of the present invention may be hair tonics, leave-on hair products such as treatment, and styling products, rinse-off hair products such as shampoos, pre-wash product, co-wash product, and personal cleansing products, and treatment products; and any other form that may be applied to hair or skin.

The dimensions and values disclosed herein are not to be understood as being strictly limited to the exact numerical values recited. Instead, unless otherwise specified, each such dimension is intended to mean both the recited value and a functionally equivalent range surrounding that value. For example, a dimension disclosed as “40 mm” is intended to mean “about 40 mm.”

Every document cited herein, including any cross referenced or related patent or application and any patent application or patent to which this application claims priority or benefit thereof, is hereby incorporated herein by reference in its entirety unless expressly excluded or otherwise limited. The citation of any document is not an admission that it is prior art with respect to any invention disclosed or claimed herein or that it alone, or in any combination with any other reference or references, teaches, suggests or discloses any such invention. Further, to the extent that any meaning or definition of a term in this document conflicts with any meaning or definition of the same term in a document incorporated by reference, the meaning or definition assigned to that term in this document shall govern.

While particular embodiments of the present invention have been illustrated and described, it would be obvious to those skilled in the art that various other changes and modifications can be made without departing from the spirit and scope of the invention. It is therefore intended to cover in the appended claims all such changes and modifications that are within the scope of this invention. 

What is claimed is:
 1. A personal care composition comprising: a) azoxystrobin in an amount from about 0.02% to about 10%; and b) salicylic acid wherein a ratio of a:b is from about 1:1 to about 50:1; wherein there is a synergistic anti-inflammatory and/or cellular stress activity in human keratinocytes immortalized by transfection with the human telomerase reverse transcriptase gene (TERT keratinocytes).
 2. A personal care composition according to claim 1 wherein an anti-inflammatory benefit is measured as Prostaglandin E2 (PGE2) activity.
 3. A personal care composition according to claim 1 wherein the personal care composition is selected from group consisting of a shampoo, conditioner, leave-on, tonic and mixtures thereof.
 4. A personal care composition according to claim 1 wherein the salicylic acid is from about 0.1% to about 10%, by weight of the composition.
 5. A personal care composition according to claim 1 wherein the salicylic acid is 0.5% to about 2%, by weight of the composition.
 6. A method of using a personal care composition comprising a step of applying to hair or skin the personal care composition comprising: a) azoxystrobin in an amount from about 0.02% to about 10%; and b) salicylic acid; wherein a ratio of a:b is from about 1:1 to about 50:1 to provide a synergistic anti-inflammatory and/or cellular stress activity in TERT keratinocytes.
 7. A method of using a personal care composition comprising a step of applying to hair or skin a personal care composition comprising: a) azoxystrobin in an amount from about 0.02% to about 10%; and b) salicylic acid; wherein the ratio of a:b is from about 1:1 to about 50:1 to provide a synergistic anti-inflammatory and/or cellular stress activity in TERT keratinocytes wherein there is at least about a 20% reduction in PGE2 release compared to a baseline of expected percent reduction in PGE2 release as calculated by summation of PGE2 release from azoxystrobin and salicylic acid.
 8. The method according to claim 7 wherein there is at least about a 40% reduction in PGE2 release compared to the baseline.
 9. A method of providing an anti-inflammatory benefit and reducing cellular stress conditions in skin, scalp and hair, said method comprising a step of applying the personal care composition according to claim 1 to hair, scalp or skin. 